The objectives of this study are to further define and characterize the biochemical and structural changes involved in maturation of collagen in a heritable connective tissue disorder of animals, the Ehlers-Danlos syndrome, and to correlate these findings with age-related changes which occur in normal animals. The Ehlers-Danlos syndrome is an autosomal dominant trait which occurs in people, dogs, and mink and is accompanied clinically by marked decrease in tensile strength of tissues, espcially the skin. These studies will involve a major effort to converge on and define the maturation defect which results in reduced skin tensile strength. The ultimate objectives of this study are to understand the nature of this collagen maturation defect in order to provide a rational means of manipulating collagen maturation and cross-linking processes which occur in aging, wound healing, and disease processes involving connective tissue in people. Goals for the coming year include further characterization of this collagen defect in affected and nonaffected animals, including definition of the collagen solubility properties to compartmentalize the defect, collagen reduction studies to further examine the in vitro correction of the solubility effect, examination of several enzyme systems important in collagen cross-link formation and to determine their role in the genesis of this collagen cross-link defect, and initiation of in vitro skin fibroblast studies to study the appearance and collagen biosynthesis properties in fibroblast cultures from affected and control animals.